J Anesth Perioper Med. 2018;6(1):8-16. https://doi.org/10.24015/ebcmed.japm.2017.0013

Dexmedetomidine Alleviates Presurgical Anxiety-Induced Persistent Postsurgical Pain via Decreasing the Expression of Glucocorticoid Receptor

Lu Li, Zuo-Xia Zhang, Zhi-Yu Yin, Cui-E Lu, Yi-Shan Lei, Rao Sun, Yue Liu, Zheng-Liang Ma*, and Xiao-Ping Gu*

From Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing, China.

Correspondence to Dr. Zheng-Liang Ma at mazhengliang1964@nju.edu.cn or Dr. Xiao-Ping Gu at xiaopinggu@nju.edu.cn.

EBCMED ID: ebcmed.japm.2017.0013 DOI: 10.24015/ebcmed.japm.2017.0013


Abstract

Background
Preoperative anxiety can worsen postsurgical pain. Glucocorticoids play an important role in psychological anxiety and pain, but the effect of glucocorticoid receptor (GR) on persurgical anxiety-induced persistent postsurgical pain remains unknown.

Methods
Adult male Sprague Dawley rats were randomly divided into 10 groups: control group, SPS group, incision group, ‘SPS-plus-incision’ group, saline group, metyrapone group, Dexmedetomidine group 1 (10 μg/kg), Dexmedetomidine group 2 (20 μg/kg), Dexmedetomidine group 3 (40 μg/kg) and Dexmedetomidine + Corticosterone group. Single-prolonged stress (SPS) was used to induce anxiety behaviors. Intraperitoneal injection of saline and dexmedetomidine was performed at 24 h after SPS and 0.5 h before incision. Intraperitoneal injection of metyrapone (25 mg/kg) was performed at 1h before SPS. Paw withdrawal mechanical threshold (PWMT) was tested at 24 h before SPS and on 1, 4, 7, 14, 21, and 28 days after incision. Corticosterone levels were determined using ELISA. The expression of GR was determined using Western blot.

Results
The ‘SPS- plus- incision’ group decreased PWMT compared with control group and incision group from 1 to 28 days (P<0.05). SPS combined with incision increased plasma corticosterone levels compared with control group (P<0.05). A timedependent increase in GR was also observed in ‘SPS- plus- incision’ group (P<0.05). Metyrapone significantly blunted the SPS- induced persistent postsurgical pain (P<0.05). Intraperitoneal administration of dexmedetomidine inhibits SPS- induced persistent pain compared with group saline (P<0.05). The expression of GR decreased after the intraperitoneal administration of dexmedetomidine (P<0.05). Pretreatment with corticosterone blocked this effect.

Conclusions
Glucocorticoids contributed to presurgical anxiety-induced persistent postsurgical pain. Dexmedetomidine that decreased the expression of GR alleviated anxiety- induced persistent pain. These results indicated that dexmedetomidine may be an effective agent for preventing presurgical anxiety-induced persistent postoperative pain. (Funded by the National Natural Science Foundation of China and the Department of Health of Jiangsu Province, China.)

Article Type
Original Article

Declaration of Interests
No other potential conflict of interest relevant to this article was reported.

Acknowledgements
This work was supported by grants from the National Natural Science Foundation of China (81471129, 81671087, 81171048, 81171047), and the Department of Health of Jiangsu Province, China (RC2011006, XK201140).

This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.